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Biomedical subjects

E Vanninen

Publications and source records attributed to E Vanninen.

At least 19 recordsLinked to original sources

Brain serotonin reuptake did not change during one year in overtrained athletes.

Brain 5-HT neurotransmission has been described to be down-regulated in depressed people, and also suspected to be changed in overtraining state, the consequence of long-term physical overloading and stress in athletes. We studied brain serotonin (5-HT) transporter binding i.e., 5-HT reuptake with the specific radioligand (123-I-labelled 2beta-carbomethoxy-3beta[4-iodopenyl]-nortropane, Nor-beta-CIT), and with single photon emission tomography (SPET) in severely overtrained athletes and their controls at the baseline and after a one-year recovery period. Twelve overtrained (6 women and 6 men, mean age 27 yrs, range 16 - 39 yrs) and 11 healthy (6 women, 5 men, 26 yrs, 20 - 39 yrs) athletes were examined. Overtrained athletes 1) had suffered from an unexplained decrement in physical performance and fatigue for several weeks to many months and continued to have the same symptoms even after a recovery time of weeks to months, 2) had been examined to be otherwise healthy, and 3) had a suitable training history for overtraining. Nor-beta-CIT SPET was acquired 5 min, and 3, 6, and 24 h after the injection of the radioligand. 5-HT reuptake in ml/ml in midbrain (raphe nuclei) was calculated as (midbrain - cerebellum)/cerebellum. According to two-way analysis of variance, no changes inside the groups or group differences in 5-HT reuptake were found. Male athletes had significantly higher 5-HT reuptake than female athletes at the baseline (p = 0.034). The overtrained athletes were moderately depressed, while their scores in standardized Hamilton and Montgomery-Asberg Depression Rating Scales were 16 +/- 2 (mean +/- SEM, range 8 - 29) and 17 +/- 2 (7 - 28), respectively. In the CA, the scores were 6 +/- 1 (range 2 - 18) and 6 +/- 2 (1 - 19), respectively. 5-HT reuptake did not correlate with the depression scores either in the whole group or in the OA. The finding of the present study does not support the idea of long-term changes in 5-HT neurotransmission in overtraining state, in this case serotonin reuptake in midbrain, the regulating area of brain serotonin neurotransmission. Furthermore, depression of overtrained athletes may be its own variant having no correlation with 5-HT reuptake in midbrain. Sex may have effect on chronic stress response at the brain level in athletes, which may be a confusing factor in the overtraining studies, and has to be taken into consideration in the future.

Adolescent↗

Cardiac effects within 3 months of BEAC high-dose therapy in non-Hodgkin's lymphoma patients undergoing autologous stem cell transplantation.

OBJECTIVES: Limited data are available on the cardiac effects of high-dose cyclophosphamide (CY) in patients with non-Hodgkin's lymphoma (NHL). We prospectively assessed the cardiac effects of high-dose CY in 30 adult NHL patients receiving CY 6 g/m(2) as part of BEAC high-dose therapy (HDT). METHODS: Radionuclide ventriculography (RVG) and plasma natriuretic peptide (NT-proANP, NT-proBNP) measurements were performed simultaneously prior to BEAC at baseline (d - 7), 12 days (d + 12) and 3 months (m + 3) after stem cell infusion (D0). In addition to these time points, natriuretic peptides were measured 2 days before (d - 2) and 1 week (d + 7) after stem cell infusion. RESULTS: Left ventricular ejection fraction (LVEF) decreased from d - 7 (53% +/- 2%) to d + 12 (49% +/- 2%, P = 0.009). However, no significant change in cardiac diastolic function was observed. The LVEF returned towards baseline by m + 3. Plasma NT-proANP and NT-proBNP increased significantly from baseline (445 +/- 65 pmol/L and 129 +/- 33 pmol/L) to d - 2 (1,127 +/- 142 pmol/L, P < 0.001 and 624 +/- 148 pmol/L, P < 0.001, respectively). Thereafter, they started to decrease, but on d + 7 NT-proANP (404 +/- 157 pmol/L, P = 0.048) and NT-proBNP (648 +/- 125 pmol/L, P = 0.015) were still significantly higher than at baseline. On d + 12 and m + 3 they no longer differed from baseline. CONCLUSIONS: Our findings suggest that high-dose CY results in acute, subclinical systolic dysfunction in NHL patients previously treated with anthracyclines. Natriuretic peptides seem to be more sensitive than LVEF to reflect this transient cardiac effect. Serial measurements of natriuretic peptides might be a useful tool to assess cardiac effects of high-dose CY.

Adult↗

Can mechanical myotonometry or electromyography be used for the prediction of intramuscular pressure?

The aim of the study was to characterize the electromechanical properties of skeletal muscle during isometric loading as well as to assess the potential of estimating intramuscular pressure by electrical and mechanical methods. Simultaneous electromyography (EMG), mechanical myotonometry (MYO, frequency and decrement of decay) and intramuscular pressure (IMP) measurements were conducted at rest and during short-term and long-term isometric contractions in patients with chronic pain in the anterior leg or dorsal forearm. The EMG amplitude and MYO(freq) accounted significantly (24-73%, p < 0.0001) for the variations in the IMP under short-term isometric loading. The IMP, EMG and MYO(freq) increased linearly with the relative muscle load (r = 0.868-0.993, p < 0.05). Mean values of EMG amplitudes at the contraction levels of 75% and 100% maximum voluntary contraction (MVC) and MYO(freq) values at all contraction levels (0-100% MVC) were higher for subjects with pathological values of IMP than for those with IMP values in the normal range. Total changes in IMP and EMG amplitude during 1 min isometric contraction were linearly interrelated (r = 0.747, p < 0.0001). We conclude that both surface electromyography and myotonometry parameters are indicative of intramuscular pressure, but neither of these methods can be used alone to diagnose non-invasively chronic compartment syndrome with acceptable accuracy.

Adolescent↗

Cross-calibration of Lunar DPX-IQ and DPX dual-energy x-ray densitometers for bone mineral measurements in women: effect of body anthropometry.

When dual-energy X-ray absorptiometry (DXA) instruments are replaced, it is essential to determine if systematic differences in measurements occur. As a part of the Kuopio Osteoporosis Risk Factor and Prevention study (N=14,220), a group of women, aged 36 to 69 yr underwent anteroposterior lumbar spine L2 to L4 (n=89) and proximal femur scans (n=88) by the Lunar DPX and DPX-IQ, respectively, during the same visit. A high linear association (r from 0.944 to 0.989, p<0.001) between the two scanners was established for lumbar spine and proximal femur bone mineral density (BMD). The average DPX values for BMD were 1.1% and 2.0% higher than those of DPX-IQ for the lumbar spine (p<0.001) and Ward's triangle (p=0.001), respectively. Femoral neck BMD values by the DPX were 1.4% lower (p<0.001) compared to DPX-IQ. The difference between trochanter BMD results (0.1%) was not significant (p=0.809). In the femoral neck and trochanter, but not in the lumbar spine or Ward's triangle, the differences in BMD values of the two machines were found to depend on body mass index. After linear formulas based on simple and multivariate linear regression analyses were calculated, the differences were negligible, enabling objective comparison of longitudinal measurements.

Absorptiometry, Photon↗

Inducibility of life-threatening ventricular arrhythmias is related to maximum left ventricular thickness and clinical markers of sudden cardiac death in patients with hypertrophic cardiomyopathy attributable to the Asp175Asn mutation in the alpha-tropomyosin gene.

We investigated inducibility of life-threatening arrhythmias with programmed ventricular stimulation (PVS) in relation to clinical markers of sudden cardiac death (SCD) in subjects with hypertrophic cardiomyopathy (HCM) attributable to the Asp175Asn mutation in the alpha-tropomyosin gene (TPM1-Asp175Asn). PVS was performed with up to three extrastimuli and distribution of markers of SCD was evaluated in 21 adult subjects with the TPM1-Asp175Asn. Sustained polymorphic ventricular tachycardia (VT) or ventricular fibrillation (VF) was induced in seven of 21 subjects (33%). Inducible subjects had more severe left ventricular hypertrophy (LVH) and an increased number of markers of SCD (family history of SCD, syncope or presyncope, fall in systolic blood pressure (BP) during exercise, documented non-sustained VT (NSVT), and marked LVH) compared to non-inducible subjects (IVS 2.4 +/- 0.3 cm vs. 1.6 +/- 0.5 cm, P < 0.001; and two to three vs. one to two markers of SCD, P = 0.007, respectively). In conclusion, in HCM attributable to the Asp175Asn mutation in the alpha-tropomyosin gene, life-threatening arrhythmias were induced in one third of the patients. Inducibility was associated with the maximum left ventricular (LV) thickness and the number of markers of SCD, suggesting that in HCM patients with an identical causative mutation, susceptibility to ventricular arrhythmias is related to the cardiomyopathic phenotype.

Adult↗

Abnormal serotonin reuptake in an overtrained, insomnic and depressed team athlete.

The purpose of this report is to study serotonin reuptake of the brain in a severely overtrained athlete by using single-photon emission computed tomography (SPECT). A 26-year-old team athlete increased his training volume (by 200 %) and intensity markedly in a new high-level team. After two months, he started to feel continuous fatigue. He had tinnitus in his left ear, he felt disturbing palpitation and had pollacisuria. After four months, he started to suffer from insomnia. He still continued to play for another three months, after which he was unable to play. He could only sleep for 3 to 4 hours per night. Only minor abnormalities could be found in extensive physical and laboratory examinations. The athlete had a severe overtraining state. In the brain SPECT scans, using the specific radioligand for serotonin transporter imaging ( (123)I labelled 2beta-carbomethoxy-3beta-[4-iodophenyl]-nortropane), low activity areas were detected in the midbrain, anterior gingulus, and left frontal and temporo-occipital lobes. In a psychiatric examination, the patient was found to have signs of major depression, which he hardly recognized himself. We conclude, that that the severe overtraining state could have been related to decreased serotonin reuptake in the brain and signs of major depression.

Adult↗

A pitfall of metaiodobenzylguanidine scan: paraganglioma in close proximity to adrenocortical adenoma.

We report a potential pitfall of 123I-metaiodobenzylguanine (MIBG) scan. Magnetic resonance imaging performed for other reasons, showed 2.5 cm tumor in the left adrenal gland. On questioning patient had episodic palpitations, flushing and hypertension suggestive of pheochromocytoma. Urinary metanephrine level was of borderline value but serum chromogranin A level was clearly elevated. 123I-MIBG scan showed accumulation of the tracer in the upper left abdomen and the finding was suspected to be intra-adrenal pheochromocytoma. During operation two separate tumors, adrenocortical adenoma in the left adrenal gland, and another smaller, extra-adrenal paraganglioma locating very close to the adenoma, were found. Thus the positive MIBG finding was caused by a paraganglioma with the concurrent presentation of nonfunctioning adrenocortical adenoma.

3-Iodobenzylguanidine↗

Heterogeneity of cerebral blood flow in symptomatic patients undergoing carotid endarterectomy.

There is still controversy concerning which patients with asymptomatic carotid stenosis or symptomatic moderate stenosis are likely to benefit from carotid endarterectomy. The surgical candidates for carotid endarterectomy should have a high risk for stroke, but a low risk for operative complications. Therefore, new effective patient selection strategies, including haemodynamic testing, schemes of risk stratification and pre-operative cardiac testing, are under investigation. To improve haemodynamic assessment of patients with carotid artery stenosis, we evaluated a novel global cerebral blood flow (CBF) heterogeneity index at rest and after acetazolamide injection in patients undergoing carotid endarterectomy. CBF heterogeneity index was measured in 15 patients by using basal and acetazolamide enhanced 99mTc-HMPAO SPET both before and 1 month after surgery. CBF heterogeneity index was calculated as the coefficient of variation of a total of 44 cerebral regions representing mainly both ipsi- and contralateral grey matter. A high linear correlation was observed between CBF heterogeneity index and ipsilateral carotid stenosis degree (r=0.74, P=0.003). Before surgery, CBF heterogeneity index increased significantly after acetazolamide injection when compared to the basal condition (from 7.0+/-1.5 to 8.3+/-1.7%, P=0.008). This response disappeared after carotid endarterectomy. When compared to pure asymmetry of CBF (ipsi/contralateral CBF ratio), the CBF heterogeneity index seemed to reflect, more sensitively, the haemodynamic effects of carotid endarterectomy. The CBF heterogeneity index after acetazolamide injection is a sensitive marker of the haemodynamic consequences of carotid artery stenosis and its operative treatment.

Acetazolamide↗

Early decline in left ventricular ejection fraction predicts doxorubicin cardiotoxicity in lymphoma patients.

Thirty adult patients with non-Hodgkin's lymphoma were studied to evaluate prospectively the significance of early decline in left ventricular ejection fraction after low cumulative doxorubicin dose (200 mg x m(-2)) in predicting the later impairment of left ventricular function. Cardiac function was monitored with radionuclide ventriculography at baseline and after cumulative doxorubicin doses of 200, 400 and 500 mg x m(-2). Cardiotoxicity was defined as a decrease in left ventricular ejection fraction of more than 10% units to a final left ventricular ejection fraction < or =50%. Twenty-eight patients received doxorubicin > or =400 mg x m(-2) and were evaluable for cardiotoxicity. Clinical heart failure developed in two patients (7%) after a cumulative doxorubicin dose of 500 mg m(-2). Left ventricular ejection fraction decreased more than 10% absolute ejection fraction units to a final left ventricular ejection fraction < or =50% in 10 patients (36%). Left ventricular ejection fraction decreased from 56+/-1.5% to 53.6+/-1.5% (P=0.016) in patients with no cardiotoxicity, and from 60.8+/-2.4% to 41.8+/-2.0% (P<0.001) in patients with cardiotoxicity. For patients who developed cardiotoxicity, the fall in left ventricular ejection fraction after a cumulative doxorubicin dose of only 200 mg x m(-2) was highly significant (left ventricular ejection fraction 49.7+/-1.8%, P=0.001 vs baseline). In receiver operator characteristic analysis, the area under the curve for the decrease in left ventricular ejection fraction at a cumulative doxorubicin dose of 200 mg x m(-2) for predicting cardiotoxicity in all patients was 0.858. The decrease in left ventricular ejection fraction of more than 4% units after a cumulative doxorubicin dose of 200 mg x m(-2) had a 90% sensitivity and 72% specificity for predicting later cardiotoxicity. Our results show that the significant impairment of left ventricular function during doxorubicin therapy can be predicted early, already at low cumulative doxorubicin doses. This finding may be of value in identifying patients at high or low risk for the development of anthracycline cardiotoxicity.

Adult↗

Natriuretic peptides during the development of doxorubicin-induced left ventricular diastolic dysfunction.

OBJECTIVES: To investigate changes in plasma atrial natriuretic peptide (ANP), N-terminal pro-atrial natriuretic peptide (NT-pro-ANP) and brain natriuretic peptide (BNP) during the development of doxorubicin-induced left ventricular systolic and diastolic dysfunction as measured by echocardiography (ECHO). DESIGN: Prospective study. SETTING: University hospital. SUBJECTS: Twenty-eight adult patients with non-Hodgkin's lymphoma, who received doxorubicin to the cumulative dose of 400-500 mg m(-2). MAIN OUTCOME MEASURES: The relationship between plasma natriuretic peptides and systolic and diastolic ECHO indices after the cumulative doxorubicin doses of 200, 400 and 500 mg m(-2). RESULTS: Left ventricular ejection fraction (LVEF, by 2D ECHO) decreased from 58 +/- 1.7 to 52.5 +/- 1.3% (P=0.036) and fractional shortening (FS) from 34.6 +/- 1.4 to 27.8 +/- 0.9% (P=0.002). Peak E wave velocity decreased from 63.3 +/- 3.2 to 51.3 +/- 2.6 cm s(-1) (P=0.008) resulting in a statistically nonsignificant decrease in E/A ratio from 1.08 +/- 0.01 to 0.85 +/- 0.07. A significant decrease was observed in the percentage of left ventricular filling during the 1/3 of diastole (1/3FF) from 42.2 +/- 1.7 to 36.5 +/- 2.0% (P < 0.001). LV end systolic diameter increased from 32 +/- 1 to 38 +/- 1 mm (P=0.011), whereas left atrial (LA) diameter remained unchanged. Peak filling rate decreased from 4.4 +/- 0.2 to 4.0 +/- 0.2 stroke volume s(-1) (SV s(-1)) (ns). Plasma levels of ANP increased from 16.4 +/- 1.3 to 22.7 +/- 2.4 pmol L(-1) (P=0.002), NT-pro-ANP from 288 +/- 22 to 380 +/- 42 pmol L(-1) (P=0.019) and BNP from 3.3 +/- 0.4 to 8.5 +/- 2.0 pmol L(-1) (P=0.020). There was a significant inverse correlation between the decrease in FS and the increases in plasma NT-pro-ANP (r= -0.524, P=0.018) and plasma BNP (r=0.462, P=0.04) and between the decrease in PFR and the increases in plasma ANP (r= -0.457, P=0.043) and plasma NT-pro-ANP (r= -0.478, P=0.033). Furthermore, after doxorubicin therapy, significant inverse correlations were observed between E/A ratio and plasma ANP (r= -0.535, P=0.008), between E/A ratio and plasma NT-pro-ANP (r= -0.432, P=0.04) and between E/A ratio and plasma BNP (r= -0.557, P=0.006) as well as between 1/3FF and plasma BNP (r= -0.493, P=0.017). There was also a trend for correlation between LA diameter and plasma BNP (r=0.395, P=0.062) and peak E wave velocity and plasma BNP (r= -0.414, P=0.05), respectively. However, no significant correlations were observed between any of the systolic parameters and natriuretic peptide levels. CONCLUSIONS: The results of this prospective study show that during the evolution of doxorubicin-induced LV dysfunction the secretion of natriuretic peptides is more closely associated with the impairment of left ventricular diastolic filling than with the deterioration of LV systolic function.

Adult↗

The relative roles of intragenic polymorphisms of the vitamin d receptor gene in lumbar spine degeneration and bone density.

STUDY DESIGN: A retrospective cohort study. OBJECTIVES: To compare the magnitudes of the associations of TaqI polymorphisms of the vitamin D receptor gene with bone density and lumbar spine degeneration in the same sample. SUMMARY OF BACKGROUND DATA: Vitamin D receptor gene variations are associated with osteoporosis, osteoarthritis, and disc degeneration. Their role in these conditions remains poorly understood. METHODS: Bone density of the spine and femur were determined through DEXA, and lumbar disc degeneration was determined from magnetic resonance imaging assessments of signal intensity, disc narrowing, bulging, anular tears, herniations, and osteophytes. Associations between these measures and TaqI polymorphisms of the coding region of the Vitamin D receptor locus were examined in a population-based sample of 142 men. RESULTS: The strongest associations were with signal intensity and anular tears, which were worse for the subjects with tt genotypes than for those with TT genotypes in the L4-S1 spine discs. Conversely, the prevalences of disc bulges and osteophytes were lowest for the tt genotype. Bone density, disc height, and herniations did not differ significantly by genotype. CONCLUSIONS: The strongest association of Vitamin D receptor TaqI polymorphisms with degeneration in nonmineralized connective tissues suggests that the underlying mechanism of TaqI polymorphisms is not specific to bone. This study demonstrated for the first time that those with the tt genotype had more anular tears than those with the TT genotype, a finding that should stimulate further analyses of this gene in conditions that result in back pain. The apparent discrepancies of the associations of the tt genotype with lower signal intensity and more anular tears, but less bulges and osteophytes, could be explained if bulging and osteophytes primarily represented remodeling related to lifetime physical loading.

Adult↗

Reduced serotonin transporter binding in binge eating women.

RATIONALE: There is evidence that abnormalities in brain dopamine, norepinephrine and serotonin metabolism may play an important role in binge eating. Serotonin-active antidepressant drugs have also been found to decrease binge eating. OBJECTIVE: We investigated serotonin transporter binding in obese binge-eating women. Eleven obese binge-eating and seven obese control women participated in the study. The subjects were not taking any medication known to affect serotonin (5-HT) transporters. METHODS: We used single-photon emission tomography (SPECT) with the radioligand 123I-labelled nor-beta-CIT, which specifically labels 5-HT transporters. RESULTS: Obese binge-eating women showed significantly decreased 5-HT transporter binding in the mid-brain compared with obese controls (2.1 +/- 0.5 versus 2.9 +/- 0.5, respectively). CONCLUSIONS: SPECT imaging with a ligand specific for 5-HT transporters can be used to assess altered serotonin transporter binding in the living human brain. The results tentatively suggest that 5-HT transporter binding is decreased in binge-eating women.

Adult↗

Diffusion and perfusion MR imaging in acute ischemic stroke: a comparison to SPECT.

Diffusion (DWI) and perfusion (PWI) magnetic resonance imaging are relatively new methods of clinical imaging that probably can detect infarcted (DWI) and hypoperfused but still salvageable tissue (PWI) in acute human stroke. Forty-six acute stroke patients were imaged within 24 h of ictus, on the second day and after a week. SPECT was also performed on 23 patients in the acute phase (first or second day). On the first day, mean volume of hypoperfused tissue was significantly greater (P<0.001) than the infarcted tissue. The initial hypoperfusion volume correlated significantly with the final infarct size (P<0.001). The initial perfusion-diffusion mismatch correlated significantly with the infarct growth (P< or =0.001). The hypoperfusion volumes measured from PWI and SPECT correlated significantly (P<0.001). In conclusion, combined DWI and PWI is a powerful tool in evaluating the hemodynamics of acute ischemic stroke and can predict the infarct growth during 1 week.

Aged↗

Anthracycline-induced cardiomyopathy: long-term effects on myocardial cell integrity, cardiac adrenergic innervation and fatty acid uptake.

Cardiotoxicity of anthracyclines is a clinical challenge in cancer chemotherapy. Limited data is available on the physiological mechanisms responsible for anthracycline-induced heart failure or its recovery. We studied four patients with a history of severe anthracycline-induced heart failure manifested 2-116 months earlier by using radionuclide ventriculography for the measurement of left ventricular function, indium-111-antimyosin scintigraphy for the detection of myocardial cell injury and iodine-123-metaiodobenzylguanidine (MIBG) scintigraphy for the assessment of cardiac adrenergic innervation. Myocardial perfusion and fatty acid utilization were assessed with iodine-123-paraphenyl pentadecanoid acid (pPPA) and single photon emission computed tomography (SPECT). Symptoms of congestive heart failure (CHF) were still present in two patients whereas the others were asymptomatic at the time of the study. The patients who showed complete clinical recovery had normal or near normal left ventricular ejection fraction (LVEF) (47 and 52%), whereas the patients with symptoms of heart failure had low ejection fractions (21 and 31%). All patients presented with abnormal antimyosin uptake and decreased myocardial MIBG uptake. Patients with low ejection fraction tended to have higher antimyosin uptake suggesting more severe, persistent myocyte injury. All but one patient showed normal fatty acid utilization. These data suggest that patients with a history of severe anthracycline-induced cardiomyopathy have persistent myocardial cell injury and adrenergic dysfunction up to 10 years after the development of heart failure. These findings seem to be present regardless of recovery of left ventricular function.

3-Iodobenzylguanidine↗

Heart rate variability and its determinants in patients with severe or mild essential hypertension.

How cardiac autonomic nervous control is related to the severity of essential hypertension in patients receiving long-term antihypertensive therapy is not well known. The aim of this study was to examine heart rate variability (HRV), a non-invasive measure of cardiac autonomic function, in patients with long-term and medically treated mild and severe essential hypertension and healthy control subjects, and to assess the clinical determinants of HRV in these patients. Thirty-four patients with severe essential hypertension (SEHT) and 29 with mild essential hypertension (MEHT) as well as healthy age- and sex-matched control subjects were studied. HRV was assessed from 10 min ECG-recordings during paced (0.2 Hz) breathing at rest and expressed as time and frequency domain measures. In the SEHT group time (SDNN, RMSSD) and frequency domain measures (total power, low-frequency (LF) power and high-frequency (HF) power of HRV in absolute units, and LF and HF power of HRV in normalized units) of HRV were significantly lower when compared with those of the control group. The MEHT and control groups did not differ from each other with respect to time or frequency domain measures of HRV. Comparison between the hypertensive groups showed that SDNN, total power, LF power and HF power were lower in the SEHT group compared with the MEHT group (P<0.05 for all). Among hypertensive patients RR-interval, age, gender, systolic finger blood pressure and diastolic office blood pressure as well as 24-h blood pressure were significant determinants of HRV. In conclusion, we found that the severity of chronic essential hypertension seems to be related to the severity of impairment of cardiac autonomic control.

Adult↗

Comparison of echocardiography and radionuclide ventriculography in the follow-up of left ventricular systolic function in adult lymphoma patients during doxorubicin therapy.

OBJECTIVES: To compare echocardiography (ECHO) and radionuclide ventriculography (RVG) in the monitoring of left ventricular systolic function during doxorubicin therapy in adult lymphoma patients. DESIGN: Prospective study. SETTINGS: University hospital. SUBJECTS: A total of 28 adult patients who received doxorubicin to a cumulative dose of 400-500 mg m(-2). MAIN OUTCOME MEASURES: ECHO and RVG were performed at baseline and after cumulative doxorubicin doses of 200, 400 and 500 mg m(-2). RESULTS: At baseline, the mean (+/-SE) left ventricular ejection fractions (LVEF) were 58 +/- 1.3, 71 +/- 1.8 and 58 +/- 1.7% as determined by RVG, M-mode ECHO and two-dimensional (2D) ECHO, respectively. After the cumulative doxorubicin dose of 500 mg m(-2) LVEF decreased to 49.6 +/- 1.7% (RVG) (P < 0.001), 62 +/- 1.6% (M-mode) (P=0.006) and 52.5 +/- 1.3% (2D ECHO) (P=0.036). Although a significant correlation between LVEF determined by RVG and M-mode ECHO (r=0.615, P=0.002) and a trend between RVG and 2D ECHO (r=0.364, P=0.096) were observed, there were substantial differences in the results of individual patients. In the agreement analysis using the method of Bland and Altman there was a mean difference of 12% units with the upper limit of agreement +26% units and the lower limit of agreement -2.1% units for LVEF determinations with M-mode ECHO and RVG, and a mean difference of 3.3% units with upper and lower limits of agreement +19.6 and -13.1% units for LVEF determinations with 2D ECHO and RVG, respectively. CONCLUSION: We found only a moderate agreement between left ventricular systolic function determined by ECHO and RVG methods. Thus, in the follow-up of left ventricular function in adult patients during doxorubicin therapy, the guidelines based on LVEF measurement by RVG cannot be applied to ECHO. Consequently, RVG remains the method of choice in this context.

Adult↗

Neuroendocrine changes during the evolution of doxorubicin-induced left ventricular dysfunction in adult lymphoma patients.

Doxorubicin-induced cardiotoxicity was used as a model to prospectively investigate neuroendocrine changes during the development of left ventricular dysfunction. Radionuclide ventriculography, frequency domain analysis of heart rate variability (HRV), and plasma noradrenaline and natriuretic peptide measurements were performed in 27 adult lymphoma patients at baseline and after cumulative doxorubicin doses of 200, 400 and 500 mg/m(2). The left ventricular ejection fraction (LVEF) decreased from 58.1+/-1.4% to 50.3+/-1.1% (P<0.001) and 49.3+/-1.7% (P<0.001) after cumulative doxorubicin doses of 400 and 500 mg/m(2) respectively. With a doxorubicin dose of up to 400 mg/m(2) there was an increase in sympathetic tone, characterized by a decrease in the normalized high-frequency (HF(nu)) power (P=0.011), and increases in the normalized low-frequency (LF(nu)) power (P=0.011), the LF/HF ratio (P=0.021) and the plasma noradrenaline concentration (P=0.034). The decrease in LVEF was correlated with the changes in LF(nu) and HF(nu) power (r=0.540, P=0.012) and LF/HF ratio (r=-0.452, P=0.04). However, after the cumulative doxorubicin dose of 500 mg/m(2) the changes in HRV components and plasma noradrenaline levels returned towards baseline. This was accompanied by increased concentrations of plasma atrial natriuretic peptide (P=0.004) and brain natriuretic peptide (P=0.021). Our findings suggest that doxorubicin-induced left ventricular dysfunction is associated with an early change in sympathovagal balance towards sympathetic predominance. Along with further progression of left ventricular dysfunction, there is an attenuation of sympathetic tone, which may be attributable to sympatho-adrenal inhibition by increased secretion of natriuretic peptides.

Adult↗